PROJECT DESCRIPTION/ABSTRACT Candidate: Dr. Tweet’s long-term goal is to become an independent clinical investigator in the field of coronary artery disease in women. Her short-term goal is to explore the vascular, autonomic and microvascular phenotypes in women with a history of spontaneous coronary artery dissection (SCAD). To achieve these goals, Dr. Tweet will: 1) acquire the expertise required for her scientific aims; 2) improve her data analysis skills via coursework and biostatistical support; 3) develop scientific leadership skills and collaborative relationships to move this field forward. Environment: The Mayo Clinic SCAD Registry is the largest international SCAD registry. Dr. Tweet’s primary mentor, Dr. Joyner and her Career Advisory Committee have the expertise and mentorship qualities to guide Dr. Tweet’s career development as a physician-scientist. Background: SCAD is a leading cause of nonatheroembolic acute coronary syndromes in women. Most patients do not have traditional risk factors such as tobacco use, hyperlipidemia, or diabetes. Rather, peripheral arterial abnormalities such as fibromuscular dysplasia are observed in the majority of patients. SCAD is associated with stress, exercise, and pregnancy. Recurrent SCAD occurs in 10-30% of patients. Specific Aims: We will aim to assess arterial structure and mechanics (Aim #1), neurovascular function (Aim #2), and microvascular function (Aim #3) in women with SCAD. Study Design & Outcome Measures: This is a prospective study of women evaluated in the Mayo Clinic SCAD Clinic. Measurements will include arterial thickness and stiffness, sympathetic baroreflex sensitivity and autonomic responses to sympathoexcitatory to standardized stressors, and myocardial perfusion echocardiography with dobutamine stress. Relationship to Career Goals of the Candidate: The projects in the application will be instrumental for the candidate’s career development by facilitating: scientific management and leadership skills, acquisition of new research techniques, and generating interdisciplinary and multi-institutional collaborative alliances. Thus it is the next logical step in her research career progression. Relationship to the NHLBI Mission: The proposed project is consistent with the NHLBI strategic vision for understanding underlying pathophysiological mechanisms of disease and for improving study of diseases affecting women. It is consistent with the NHLBI’s interest in hypertension, sympathoexcitation and cardiovascular disease risk. It is also consistent with broader NIH goals related to training the next generation of clinical investigators.

NARRATIVE Spontaneous coronary artery dissection (SCAD) is the leading cause of nonatherothrombotic myocardial infarction in women under age 40 years, the etiology of ST-elevation myocardial infarction in 1 of 5 women under age 50 years, and a frequent cause of heart attack among pregnant women. Most patients with SCAD do not have traditional risk factors such as tobacco use, high cholesterol, diabetes, but rather, they have abnormalities in the peripheral arteries such as fibromuscular dysplasia, aneurysms, and dissections. The proposed aims of this proposal explore the vascular, autonomic, and myocardial phenotypes in women with SCAD and in doing so better understand pathophysiologic mechanisms, risk for disease, and ultimately guide approaches to improve outcomes.